Effect of 5-HT2 and 5-HT3 receptor antagonists on cholera toxin-induced fluid hypersecretion in the pig jejunum

5-Hydroxytryptamine is a mediator in cholera toxin-induced hypersecretion in the small intestine. The aim of this study was to determine the effect of the 5-hydroxytryptamine receptor antagonists ketanserin, granisetron, ondansetron and tropisetron on cholera toxin-induced hypersecretion in the pig jejunum. Hypersecretion was induced by cholera toxin in ligated jejunal loops. The antagonists were administered subcutaneously at a dose of 100 micrograms/kg. Furthermore, the effect of intraluminally instilled ondansetron was studied. None of the antagonists altered basal absorption or caused fluid hypersecretion. Cholera toxin caused a dose-dependent electrolyte and fluid hypersecretion. The apparent maximal effect, 6.8 +/- 0.4 mg fluid x mg dry loop-1, was reduced by ondansetron, granisetron and tropisetron by about 40%, 30%, and 20%, respectively, whereas ketanserin had no effect. Intraluminal ondansetron reduced the effect of cholera toxin by about 50%. These results demonstrate that 5-hydroxytryptamine3 antagonists administered subcutaneously reduce the cholera toxin-induced hypersecretion in the pig jejunum. Finally, the results support species differences with respect to the antagonistic effect of the tested drugs in cholera toxin-induced hypersecretion.